tbuckley/cabot-search huggingface dataset:
Effects of exercise interventions on cognitive functions in healthy populations: A systematic review and meta-analysis
Authors: Minggang Zhang, Jiafeng Jia, Yang Yang, Lepu Zhang, Xiaochun Wang
Journal: Ageing Research Reviews (2023)

Chronic exercise intervention is a non-pharmacological therapy suggested to improve cognitive function in various populations. However, few meta-analyses have assessed the cognitive benefits associated with all FITT-VP variables (exercise frequency, intensity, bout duration time, type, volume or total intervention length, and progression) in healthy populations by age. Thus, this meta-analysis assessed the effects of each FITT-VP variable on cognitive function in healthy children, adults, and older adults. This study followed PRISMA guidelines. After searching PubMed and the Web of Science, we included 54 randomized controlled trials to examined the effects of FITT-VP variables on five cognitive domains: global cognition, executive function, memory, attention, and information processing. Moderation analyses assessed the effects by age and by each exercise variables. Exercise benefitted overall cognition and all subcognitive domains. Aerobic and resistance exercise showed the greatest benefits on global cognition and executive function respectively, whereas mind-body exercise benefitted memory. Among all populations, older adults showed the greatest benefits of exercise on global cognition, executive function, and memory compared with controls. Additional studies are needed to assess the effects of exercise on attention and information processing. This meta-analysis offers new insights on the relationships between cognition and FITT-VP exercise variables in healthy populations.
Biomarkers of response to topical crisaborole in patients with mild/moderate pediatric atopic dermatitis from minimally invasive tape strip transcriptome
Authors: Anna B. Fishbein, Janak Mukherji, Michael Demczuk, Brooke Buranosky, Jack Osborn, Crista Moreno, Dominic LaRoche, Amy S. Paller, Kurt Q. Lu
Journal: Journal of the American Academy of Dermatology (2023)
Mechano-Sensor for proprioception inspired by ultrasensitive trigger hairs of Venus flytrap
Authors: Qian Wang, Zezhong Lu, Deshan Wang, Kejun Wang
Journal: Cyborg and Bionic Systems (2023)

Mechanosensors, as the core component of a proprioceptive system, can detect many types of mechanical signals in their surroundings, such as force signals, displacement signals, and vibration signals. It is understandable that the development of an all-new mechanosensory structure that can be widely used is highly desirable. This is because it can markedly improve the detection performance of mechanosensors. Coincidentally, in nature, optimized microscale trigger hairs of Venus flytrap are ingeniously used as a mechanosensory structure. These trigger hairs are utilized for tactile mechanosensilla to efficiently detect external mechanical stimuli. Biological trigger hair-based mechanosensilla offer an all-new bio-inspired strategy. This strategy utilizes the notch structure and variable stiffness to enhance the perceptual performance of mechanosensors. In this study, the structure-performance-application coupling relationship of trigger hair-based mechanosensors is explored through experiment and analysis. An artificial trigger hair-based mechanosensor is developed by mimicking the deformation properties of the Venus flytrap trigger hair. This bio-inspired mechanosensor shows excellent performance in terms of mechanical stability, response time, and sensitivity to mechanical signals.
A Domain Generalization and Residual Network Based Emotion Recognition from Physiological Signals
Authors: Junnan Li, Jiang Li, Xiaoping Wang, Xin Zhan, Zhigang Zeng
Journal: Cyborg and Bionic Systems (2023)

Emotion recognition from physiological signals (ERPS) has drawn tremendous attention and can be potentially applied to numerous fields. Since physiological signals are nonstationary time series with high sampling frequency, it is challenging to directly extract features from them. Additionally, there are 2 major challenges in ERPS: (a) how to adequately capture the correlations between physiological signals at different times and between different types of physiological signals and (b) how to effectively minimize the negative effect caused by temporal covariate shift (TCS). To tackle these problems, we propose a domain generalization and residual network-based approach for emotion recognition from physiological signals (DGR-ERPS). We first pre-extract time- and frequency-domain features from the original time series to compose a new time series. Then, in order to fully extract the correlation information of different physiological signals, these time series are converted into 3D image data to serve as input for a residual-based feature encoder (RBFE). In addition, we introduce a domain generalization-based technique to mitigate the issue posed by TCS. We have conducted extensive experiments on 2 real-world datasets, and the results indicate that our DGR-ERPS achieves superior performance under both TCS and non-TCS scenarios.
Real-world effectiveness of immune checkpoint inhibitors and BRAF/MEK inhibitors among veteran patients with cutaneous melanoma
Authors: Daniel Y. Kim, Susan M. Swetter, Linden Huhmann, Matthew P. Dizon, Jacqueline M. Ferguson, Thomas F. Osborne, Allyson C. Spence, Amina Ziad, Nathanael Fillmore, Rebecca I. Hartman
Journal: Journal of the American Academy of Dermatology (2023)
Blockage of EGFR/AKT and mevalonate pathways synergize the antitumor effect of temozolomide by reprogramming energy metabolism in glioblastoma
Authors: Xiaoteng Cui, Jixing Zhao, Guanzhang Li, Chao Yang, Shixue Yang, Qi Zhan, Junhu Zhou, Yunfei Wang, Menglin Xiao, Biao Hong, Kaikai Yi, Fei Tong, Yanli Tan, Hu Wang, Qixue Wang, Tao Jiang, Chuan Fang, Chunsheng Kang
Journal: Cancer Communications (2023)

Abstract Background Metabolism reprogramming plays a vital role in glioblastoma (GBM) progression and recurrence by producing enough energy for highly proliferating tumor cells. In addition, metabolic reprogramming is crucial for tumor growth and immune‐escape mechanisms. Epidermal growth factor receptor ( EGFR ) amplification and EGFR‐vIII mutation are often detected in GBM cells, contributing to the malignant behavior. This study aimed to investigate the functional role of the EGFR pathway on fatty acid metabolism remodeling and energy generation. Methods Clinical GBM specimens were selected for single‐cell RNA sequencing and untargeted metabolomics analysis. A metabolism‐associated RTK‐fatty acid‐gene signature was constructed and verified. MK‐2206 and MK‐803 were utilized to block the RTK pathway and mevalonate pathway induced abnormal metabolism. Energy metabolism in GBM with activated EGFR pathway was monitored. The antitumor effect of Osimertinib and Atorvastatin assisted by temozolomide (TMZ) was analyzed by an intracranial tumor model in vivo. Results GBM with high EGFR expression had characteristics of lipid remodeling and maintaining high cholesterol levels, supported by the single‐cell RNA sequencing and metabolomics of clinical GBM samples. Inhibition of the EGFR/AKT and mevalonate pathways could remodel energy metabolism by repressing the tricarboxylic acid cycle and modulating ATP production. Mechanistically, the EGFR/AKT pathway upregulated the expressions of acyl‐CoA synthetase short‐chain family member 3 (ACSS3), acyl‐CoA synthetase long‐chain family member 3 (ACSL3), and long‐chain fatty acid elongation‐related gene ELOVL fatty acid elongase 2 (ELOVL2) in an NF‐κB‐dependent manner. Moreover, inhibition of the mevalonate pathway reduced the EGFR level on the cell membranes, thereby affecting the signal transduction of the EGFR/AKT pathway. Therefore, targeting the EGFR/AKT and mevalonate pathways enhanced the antitumor effect of TMZ in GBM cells and animal models. Conclusions Our findings not only uncovered the mechanism of metabolic reprogramming in EGFR‐activated GBM but also provided a combinatorial therapeutic strategy for clinical GBM management.
Bioresponsive and immunotherapeutic nanomaterials to remodel tumor microenvironment for enhanced immune checkpoint blockade
Authors: Tianxu Fang, Xiaona Cao, Li Wang, Mo Chen, Yueyang Deng, Guojun Chen
Journal: Bioactive Materials (2023)

Immune checkpoint blockade (ICB) therapy is a revolutionary approach to treat cancers, but still have limited clinical applications. Accumulating evidence pinpoints the immunosuppressive characteristics of the tumor microenvironment (TME) as one major obstacle. The TME, characterized by acidity, hypoxia and elevated ROS levels, exerts its detrimental effects on infiltrating anti-tumor immune cells. Here, we developed a TME-responsive and immunotherapeutic catalase-loaded calcium carbonate nanoparticles (termed as CAT@CaCO3 NPs) as the simple yet versatile multi-modulator for TME remodeling. CaCO3 NPs can consume protons in the acidic TME to normalize the TME pH. CAT catalyzed the decomposition of ROS and thus generated O2. The released Ca2+ led to Ca2+ overload in the tumor cells which then triggered the release of damage-associated molecular patterns (DAMP) signals to initiate anti-tumor immune responses, including tumor antigen presentation by dendritic cells. Meanwhile, CAT@CaCO3 NPs-induced immunosupportive TME also promoted the polarization of the M2 tumor-associated macrophages to the M1 phenotype, further enhancing tumor antigen presentation. Consequently, T cell-mediated anti-tumor responses were activated, the efficacy of which was further boosted by aPD-1 immune checkpoint blockade. Our study demonstrated that local treatment of CAT@CaCO3 NPs and aPD-1 combination can effectively evoke local and systemic anti-tumor immune responses, inhibiting the growth of treated tumors and distant diseases.
Engineering the next generation of theranostic biomaterials with synthetic biology
Authors: Xiang Wang, Qianyi Liang, Yixuan Luo, Jianwen Ye, Yin Yu, Fei Chen
Journal: Bioactive Materials (2023)

Biomaterials have evolved from inert materials to responsive entities, playing a crucial role in disease diagnosis, treatment, and modeling. However, their advancement is hindered by limitations in chemical and mechanical approaches. Synthetic biology enabling the genetically reprograming of biological systems offers a new paradigm. It has achieved remarkable progresses in cell reprogramming, engineering designer cells for diverse applications. Synthetic biology also encompasses cell-free systems and rational design of biological molecules. This review focuses on the application of synthetic biology in theranostics, which boost rapid development of advanced biomaterials. We introduce key fundamental concepts of synthetic biology and highlight frontier applications thereof, aiming to explore the intersection of synthetic biology and biomaterials. This integration holds tremendous promise for advancing biomaterial engineering with programable complex functions.
ASXL1 mutation is a novel risk factor for bleeding in Philadelphia-negative myeloproliferative neoplasms
Authors: Hassan Awada, Manasa Bhatta, Han Yu, Wenyan Ji, Surui Hou, Tara Cronin, Sheeba Ba Aqeel, Arya Mariam Roy, Muhammad Salman Faisal, Peter Kouides, John Mascarenhas, Elizabeth A. Griffiths, Amro Elshoury
Journal: Leukemia (2023)
Phase Ia/b Study of Giredestrant ± Palbociclib and ± Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor–Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer
Authors: Komal L. Jhaveri, Meritxell Bellet, Nicholas C. Turner, Sherene Loi, Aditya Bardia, Valentina Boni, Joohyuk Sohn, Tomas G. Neilan, Rafael Villanueva-Vázquez, Peter Kabos, Laura García-Estévez, Elena López-Miranda, J. Alejandro Pérez-Fidalgo, Jose M. Pérez-García, Jiajie Yu, Jill Fredrickson, Heather M. Moore, Ching-Wei Chang, John W. Bond, Jennifer Eng-Wong, Mary R. Gates, Elgene Lim
Journal: Clinical Cancer Research (2023)

Giredestrant is an investigational next-generation, oral, selective estrogen receptor antagonist and degrader for the treatment of estrogen receptor-positive (ER+) breast cancer. We present the primary analysis results of the phase Ia/b GO39932 study (NCT03332797).
Cost of Pacing in Pediatric Patients With Postoperative Heart Block After Congenital Heart Surgery
Authors: Abhijit Mondal, Minkyoung Yoo, Stephanie Tuttle, Douglas Mah, Richard Nelson, Frank B. Sachse, Robert Hitchcock, Aditya K. Kaza
Journal: JAMA Network Open (2023)

Surgical correction of congenital heart defects (CHDs) has improved the lifespan and quality of life of pediatric patients. The number of congenital heart surgeries (CHSs) in children has grown continuously since the 1960s. This growth has been accompanied by a rise in the incidence of postoperative heart block requiring permanent pacemaker (PPM) implantation.
Combined Vorinostat and Chloroquine Inhibit Sodium–Iodide Symporter Endocytosis and Enhance Radionuclide Uptake <i>In Vivo</i>
Authors: Martin L. Read, Katie Brookes, Ling Zha, Selvambigai Manivannan, Jana Kim, Merve Kocbiyik, Alice Fletcher, Caroline M. Gorvin, George Firth, Gilbert O. Fruhwirth, Juan P. Nicola, Sissy Jhiang, Matthew D. Ringel, Moray J. Campbell, Kavitha Sunassee, Philip J. Blower, Kristien Boelaert, Hannah R. Nieto, Vicki E. Smith, Christopher J. McCabe
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Patients with aggressive thyroid cancer are frequently failed by the central therapy of ablative radioiodide (RAI) uptake, due to reduced plasma membrane (PM) localization of the sodium/iodide symporter (NIS). We aimed to understand how NIS is endocytosed away from the PM of human thyroid cancer cells, and whether this was druggable in vivo. Experimental Design: Informed by analysis of endocytic gene expression in patients with aggressive thyroid cancer, we used mutagenesis, NanoBiT interaction assays, cell surface biotinylation assays, RAI uptake, and NanoBRET to understand the mechanisms of NIS endocytosis in transformed cell lines and patient-derived human primary thyroid cells. Systemic drug responses were monitored via 99mTc pertechnetate gamma counting and gene expression in BALB/c mice. Results: We identified an acidic dipeptide within the NIS C-terminus that mediates binding to the σ2 subunit of the Adaptor Protein 2 (AP2) heterotetramer. We discovered that the FDA-approved drug chloroquine (CQ) modulates NIS accumulation at the PM in a functional manner that is AP2 dependent. In vivo, CQ treatment of BALB/c mice significantly enhanced thyroidal uptake of 99mTc pertechnetate in combination with the histone deacetylase (HDAC) inhibitor vorinostat/SAHA, accompanied by increased thyroidal NIS mRNA. Bioinformatic analyses validated the clinical relevance of AP2 genes with disease-free survival in RAI-treated DTC, enabling construction of an AP2 gene–related risk score classifier for predicting recurrence. Conclusions: NIS internalization is specifically druggable in vivo. Our data, therefore, provide new translatable potential for improving RAI therapy using FDA-approved drugs in patients with aggressive thyroid cancer. See related commentary by Lechner and Brent, p. 1220
Adverse events after first and second doses of COVID-19 vaccination in England: a national vaccine surveillance platform self-controlled case series study
Authors: Ruby SM Tsang, Utkarsh Agrawal, Mark Joy, Rachel Byford, Chris Robertson, Sneha N Anand, William Hinton, Nikhil Mayor, Debasish Kar, John Williams, William Victor, Ashley Akbari, Declan T Bradley, Siobhan Murphy, Dermot O’Reilly, Rhiannon K Owen, Antony Chuter, Jillian Beggs, Gary Howsam, Aziz Sheikh, FD Richard Hobbs, Simon de Lusignan
Journal: Journal of the Royal Society of Medicine (2023)

Objectives To estimate the incidence of adverse events of interest (AEIs) after receiving their first and second doses of coronavirus disease 2019 (COVID-19) vaccinations, and to report the safety profile differences between the different COVID-19 vaccines. Design We used a self-controlled case series design to estimate the relative incidence (RI) of AEIs reported to the Oxford-Royal College of General Practitioners national sentinel network. We compared the AEIs that occurred seven days before and after receiving the COVID-19 vaccinations to background levels between 1 October 2020 and 12 September 2021. Setting England, UK. Participants Individuals experiencing AEIs after receiving first and second doses of COVID-19 vaccines. Main outcome measures AEIs determined based on events reported in clinical trials and in primary care during post-license surveillance. Results A total of 7,952,861 individuals were vaccinated with COVID-19 vaccines within the study period. Among them, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs. Within the first seven days post-vaccination, 4.85% of all the AEIs were reported. There was a 3–7% decrease in the overall RI of AEIs in the seven days after receiving both doses of Pfizer-BioNTech BNT162b2 (RI = 0.93; 95% CI: 0.91–0.94) and 0.96; 95% CI: 0.94–0.98), respectively) and Oxford-AstraZeneca ChAdOx1 (RI = 0.97; 95% CI: 0.95–0.98) for both doses), but a 20% increase after receiving the first dose of Moderna mRNA-1273 (RI = 1.20; 95% CI: 1.00–1.44)). Conclusions COVID-19 vaccines are associated with a small decrease in the incidence of medically attended AEIs. Sentinel networks could routinely report common AEI rates, which could contribute to reporting vaccine safety.
Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis
Authors: Michelle N. Rheault, Charles E. Alpers, Jonathan Barratt, Stewart Bieler, Pietro Canetta, Dong-Wan Chae, Gaia Coppock, Ulysses Diva, Loreto Gesualdo, Hiddo J.L. Heerspink, Jula K. Inrig, Gianna M. Kirsztajn, Donald Kohan, Radko Komers, Laura A. Kooienga, Kenneth Lieberman, Alex Mercer, Irene L. Noronha, Vlado Perkovic, Jai Radhakrishnan, William Rote, Brad Rovin, Vladimir Tesar, Hernán Trimarchi, James Tumlin, Muh Geot Wong, Howard Trachtman
Journal: New England Journal of Medicine (2023)

An unmet need exists for focal segmental glomerulosclerosis (FSGS) treatment. In an 8-week, phase 2 trial, sparsentan, a dual endothelin–angiotensin receptor antagonist, reduced proteinuria in patients with FSGS. The efficacy and safety of longer-term treatment with sparsentan for FSGS are unknown. Download a PDF of the Research Summary. In this phase 3 trial, we enrolled patients with FSGS (without known secondary causes) who were 8 to 75 years of age; patients were randomly assigned to receive sparsentan or irbesartan (active control) for 108 weeks. The surrogate efficacy end point assessed at the prespecified interim analysis at 36 weeks was the FSGS partial remission of proteinuria end point (defined as a urinary protein-to-creatinine ratio of ≤1.5 [with protein and creatinine both measured in grams] and a >40% reduction in the ratio from baseline). The primary efficacy end point was the estimated glomerular filtration rate (eGFR) slope at the time of the final analysis. The change in eGFR from baseline to 4 weeks after the end of treatment (week 112) was a secondary end point. Safety was also evaluated. A total of 371 patients underwent randomization: 184 were assigned to receive sparsentan and 187 to receive irbesartan. At 36 weeks, the percentage of patients with partial remission of proteinuria was 42.0% in the sparsentan group and 26.0% in the irbesartan group (P=0.009), a response that was sustained through 108 weeks. At the time of the final analysis at week 108, there were no significant between-group differences in the eGFR slope; the between-group difference in total slope (day 1 to week 108) was 0.3 ml per minute per 1.73 m2 of body-surface area per year (95% confidence interval [CI], −1.7 to 2.4), and the between-group difference in the slope from week 6 to week 108 (i.e., chronic slope) was 0.9 ml per minute per 1.73 m2 per year (95% CI, −1.3 to 3.0). The mean change in eGFR from baseline to week 112 was −10.4 ml per minute per 1.73 m2 with sparsentan and −12.1 ml per minute per 1.73 m2 with irbesartan (difference, 1.8 ml per minute per 1.73 m2; 95% CI, −1.4 to 4.9). Sparsentan and irbesartan had similar safety profiles, and the frequency of adverse events was similar in the two groups. Among patients with FSGS, there were no significant between-group differences in eGFR slope at 108 weeks, despite a greater reduction in proteinuria with sparsentan than with irbesartan. (Funded by Travere Therapeutics; DUPLEX ClinicalTrials.gov number, NCT03493685.) QUICK TAKE VIDEO SUMMARYSparsentan in Focal Segmental Glomerulosclerosis 02:05
Sleep and Burnout Among Health Care Professionals—The Role of the Individual
Authors: Dave W. Lu
Journal: JAMA Network Open (2023)

Ari Shechter, PhD; Tsion Firew, MD, MPH; Maody Miranda, MA; Nakesha Fray, MPH; Allison A. Norful, PhD, RN, ANP-BC; Alvis Gonzalez, BS; Bernard P. Chang, MD, PhD
Non‐invasive omics analysis delineates molecular changes in water‐only fasting and its sex‐discriminating features in metabolic syndrome patients
Authors: Yanyu Jiang, Zhimei Tang, Xiaogang Zhu, Biying Xiao, Hechuan Tian, Xingxing Lei, Huan Peng, Jun Qin, Yanmei Zhang, Robert M. Hoffman, Xiaorong Hu, Qiu Chen, Guang Ji, Lijun Jia
Journal: MedComm (2023)

Fasting has been grown in popularity with multiple potential benefits. However, very few studies dynamically monitor physiological and pathological changes during long-term fasting using noninvasive methods. In the present study, we recruited 37 individuals with metabolic syndrome to engage in a 5-day water-only fasting regimen, and simultaneously captured the molecular alterations through urinary proteomics and metabolomics. Our findings reveal that water-only fasting significantly mitigated metabolic syndrome-related risk markers, such as body weight, body mass index, abdominal circumference, blood pressure, and fasting blood glucose levels in metabolic syndrome patients. Indicators of liver and renal function remained within the normal range, with the exception of uric acid. Notably, inflammatory response was inhibited during the water-only fasting period, as evidenced by a decrease in the human monocyte differentiation antigen CD14. Intriguingly, glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation underwent a sex-dependent reprogramming throughout the fasting period, whereby males exhibited a greater upregulation of carbohydrate metabolism-related enzymes than females. This disparity may be attributed to evolutionary pressures. Collectively, our study sheds light on the beneficial physiological effects and novel dynamic molecular features associated with fasting in individuals with metabolic syndrome using noninvasive methods.